Leon M B, Rosing D R, Bonow R O, Epstein S E
Am J Cardiol. 1985 Jan 25;55(3):69B-80B. doi: 10.1016/0002-9149(85)90615-0.
Combination therapy using calcium-channel blockers and beta blockers in patients with refractory chronic stable angina has gained much popularity, but remains highly controversial because of the potential for serious additive deleterious hemodynamic or electrophysiologic reactions. In studies involving patients with preserved left ventricular function receiving chronic oral beta blockers, short-term administration of intravenous verapamil has been shown to cause a further lowering in heart rate and blood pressure while prolonging atrioventricular node conduction; additive cardiodepressant effects were noted, including a tendency toward increased left and right heart filling pressures. Nifedipine, on the other hand, when added acutely to beta blockers, causes an increase in heart rate, a decrease in blood pressure and either no change or a slight improvement in most cardiac performance variables. Controlled, double-blind clinical trials have demonstrated that combinations of calcium-channel blockers and beta blockers result in augmented symptom benefit compared with either drug class alone. The predominant mechanism responsible for such improvement is increased lowering of myocardial oxygen demand by virtue of additive diminution in heart rate, blood pressure and, consequently, pressure-rate product both at rest and during exercise. Verapamil (and possibly diltiazem) plus beta blockers appears to have the greatest therapeutic efficacy but also the highest frequency of harmful adverse cardiac effects, whereas nifedipine plus beta blockers is generally safer but also less efficacious. Factors that should be carefully considered by clinicians contemplating combination therapy are the choice of calcium-channel blocker, the dose of calcium-channel blocker and beta blocker, the presence of antecedent left ventricular dysfunction or conduction system disease and the possibility of drug interactions. Concomitant calcium-channel blocker and beta-blocker therapy is an important contribution to the pharmacologic management of resistant patients who remain symptomatic during single drug treatment. However, the possibility of additive adverse cardiac effects mandates careful patient selection and close clinical monitoring.
在难治性慢性稳定性心绞痛患者中，使用钙通道阻滞剂和β受体阻滞剂的联合治疗已颇受欢迎，但由于可能产生严重的累加有害血流动力学或电生理反应，仍存在高度争议。在涉及接受慢性口服β受体阻滞剂且左心室功能保留的患者的研究中，静脉注射维拉帕米的短期给药已显示会导致心率和血压进一步降低，同时延长房室结传导；注意到有累加的心脏抑制作用，包括左右心充盈压升高的趋势。另一方面，硝苯地平在急性添加到β受体阻滞剂时，会导致心率增加、血压降低，并且大多数心脏功能变量无变化或略有改善。对照的双盲临床试验表明，与单独使用任何一类药物相比，钙通道阻滞剂和β受体阻滞剂联合使用能增强症状改善效果。导致这种改善的主要机制是通过累加降低静息和运动时的心率、血压以及因此的压力 - 心率乘积，从而增加心肌需氧量的降低。维拉帕米（可能还有地尔硫䓬）加β受体阻滞剂似乎具有最大的治疗效果，但有害的不良心脏效应发生率也最高，而硝苯地平加β受体阻滞剂通常更安全但效果也较差。考虑联合治疗的临床医生应仔细考虑的因素包括钙通道阻滞剂的选择、钙通道阻滞剂和β受体阻滞剂的剂量、先前存在的左心室功能障碍或传导系统疾病以及药物相互作用的可能性。钙通道阻滞剂和β受体阻滞剂的联合治疗是对单药治疗期间仍有症状的耐药患者药物管理的重要贡献。然而，累加不良心脏效应的可能性要求仔细选择患者并密切进行临床监测。
